This invention relates to a process for submitting to conditions of microgravity a system--more particularly made of a cell culture--normally submitted to the influence of a gravitational field.
The invention also relates to an apparatus for implementing this process.
Biological processes in space constitute a new discipline in the field of biotechnologies and possess an ever growing significance for industrialized countries, particularly for the preparation of pharmaceutical products.
As to the potential benefits to be gained from the culture, purification and transformation of animal and human cells, as well as from products obtained through these operations, under microgravity conditions, these have been and will be assessed during a special research program carried out by NASA, ESA, industrial Companies and Research Laboratories on board SPACELAB.
In particular, industry's attention is principally focused on the development of (protein, cell, &c) separation techniques, and culture techniques for cells such as microorganisms or animal and human cells.
Heretofore experiments carried out on animal and human cells have shown, unambiguously, that living cells are sensitive to gravity, and that under microgravity conditions their rate of cell division (proliferation) is altered by comparison with the phenomenon taking place in a gravitational field.
Cells with motility, such as Paramecium aurelia, possess, under microgravity conditions, a higher proliferation rate but a lower amount of synthesized proteins, whereas cells without motility, such as lymphocytes, possess, under microgravity conditions, a lower proliferation rate and a higher amount of synthesized interferon.
It will thus be readily understood that a reduced proliferation, combined with a smaller energy consumption (the latter resulting from the fact that the cells do not need to make any effort against gravity), could open the way to an increased production, under microgravity conditions, of cell products, notably necessary to the pharmaceutical industry.
Therefore, it is also understood that, if it were possible to produce microgravity conditions in plants submitted to the earth's gravitational field, scientific research as well as industrial applications of cell culture techniques under these conditions would be notably simplified.
But as concerns submitting a system, which to start with may be any system, to microgravity conditions, one must note that these conditions can only be obtained if said system is in a state of free fall, that is only if the gravity force is not balanced by another force (whatever the nature of the balancing force).
To this time different methods are known for submitting an unspecified system to conditions of microgravity during a given period; in particular the following system is known:
a) having the system fall from the top of a tower called zero gravity tower;
b) putting the system inside an aeroplane following the trajectory of a ballistic flight (see paper in ESA Bulletin, n.degree. 42, May 1986, Parabolic Aircraft Flights--An effective Tool in preparing Microgravity Experiments`).
c) putting the system in a missile following the trajectory of a ballistic flight, the greater part of this trajectory being situated outside the atmosphere;
d) putting the system into orbit around the earth.
As to the time interval of microgravity conditions obtained with the first three methods, a)-c), this is about 5 seconds, 30 seconds, and 10 minutes, respectively.
However only the fourth method mentioned under d) ensures as a rule continued microgravity conditions.
Knowing that cell cultures generally require incubation periods from several days to several weeks, the fourth method is clearly the only one with which this culture can be made under actual microgravity conditions during the whole incubation period.
To this time only one machine is known to be able, only up to a point, to simulate continuous duration microgravity conditions. This is CLINOSTAT, whose principle relies on the rotation of plants or cells around a horizontal axis so as to modify continuously the direction of the gravity of the gravity acceleration vector and to `disorientate` them, in other words to make them unable to feel the influence of a gravitational field acting in a precise direction.
Two variants of this machine have been used in basic research:
1) Low speed rotation CLINOSTAT, largely used for studying the behaviour of plants under microgravity conditions (see Proc. 2nd European Symposium on Life Sciences Research in Space, Porz Wahn, Germany 4-6 June 1984 (ESA SP-212-August 1984)), and
2) High speed rotation CLINOSTAT, recently used for studying the behaviour of cells and small organisms under microgravity conditions (see publication mentioned under 1 above as well as Proceedings of a workshop on Space Biology, Cologne, Germany 9-11 Mar. 1983 (ESA SP-206, May 1983)).
However these machines present two major drawbacks:
a') they do not ensure actual microgravity conditions,
b') when they are used for studying cell behaviour, the rotating tube which makes up each type of machine must possess a very small diameter in order to minimize centrifugal acceleration (the latter naturally acting in a continuous manner).
Apart from the fact that results obtained with a CLINOSTAT often differ widely from results obtained during space missions (see particularly The Physiologist, Vol. 28, No 6, Suppl., 1985, and The Physiologist, Vol. 28, No 6, Suppl., 1985), which is probably due to the drawback mentioned under a'), it must be stressed that the constraint mentioned under b' (and representing another CLINOSTAT drawback) deprives this machine from the necessary experimental flexibility and prevents some of its large scale applications.